Taxol is one of the most promising anti-cancer drugs currently under investigation. Clinical trials have proven the usefulness of this compound especially in cancers of the breast and ovarian systems. The main factor limiting a more widespread use of taxol is its availability. In nature it is found exclusively in the plant genus Taxus and in particular in the U.S., the wild species Taxus brevifolia (Pacific yew). In this project we seek to investigate those factors in the plant and its microbial environment that influence taxol production. Initially, we will do this using an in vitro system involving inner bark pieces that biosynthesize taxol. This test system has already been proven. We now seek to more completely explore, isolate and identify those factors from endophytic fungi that affect taxol production. Preliminary data unequivocally have shown a positive influence of such compounds as fungal elicitors, gibberellic acid and chloro- choline chloride on taxol production. Also, it is also conceivable that one or more endophytic fungi or bacteria from Taxus are capable of producing taxol or a related taxane. We have been successful in isolating at least 50 fungi from aseptically treated inner bark. We plan to systematically screen these organisms for taxol (taxane) production. Field studies, in vitro production of taxol by a bark reactor, and other biological and chemical factors controlling taxol production will be studied.